title: Inhibition of the Fe(III)-catalyzed dopamine oxidation by ATP and its relevance to oxidative stress in Parkinson's disease.
abstract: Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic cells, which implicates a role of dopamine (DA) in the etiology of PD. A possible DA degradation pathway is the Fe(III)-catalyzed oxidation of DA by oxygen, which produces neuronal toxins as side products. We investigated how ATP, an abundant and ubiquitous molecule in cellular milieu, affects the catalytic oxidation reaction of dopamine. For the first time, a unique, highly stable DA-Fe(III)-ATP ternary complex was formed and characterized in vitro. ATP as a ligand shifts the catecholate-Fe(III) ligand metal charge transfer (LMCT) band to a longer wavelength and the redox potentials of both DA and the Fe(III) center in the ternary complex. Remarkably, the additional ligation by ATP was found to significantly reverse the catalytic effect of the Fe(III) center on the DA oxidation. The reversal is attributed to the full occupation of the Fe(III) coordination sites by ATP and DA, which blocks O2 from accessing the Fe(III) center and its further reaction with DA. The biological relevance of this complex is strongly implicated by the identification of the ternary complex in the substantia nigra of rat brain and its attenuation of cytotoxicity of the Fe(III)-DA complex. Since ATP deficiency accompanies PD and neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) induced PD, deficiency of ATP and the resultant impairment toward the inhibition of the Fe(III)-catalyzed DA oxidation may contribute to the pathogenesis of PD. Our finding provides new insight into the pathways of DA oxidation and its relationship with synaptic activity.
authors.affiliation: Department of Chemistry and Biochemistry, California State University, Los Angeles , Los Angeles, California 90032, United States.
authors.forename: Dianlu
authors.initials: D
authors.lastname: Jiang
authors.forename: Shuyun
authors.initials: S
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Bingrong
authors.initials: B
authors.lastname: Ding
authors.forename: Bingqing
authors.initials: B
authors.lastname: Zhao
authors.forename: Gargey
authors.initials: G
authors.lastname: Yagnik
authors.forename: Feimeng
authors.initials: F
authors.lastname: Zhou
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002384:Catalysis; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D005290:Ferric Compounds / Q000037:antagonists & inhibitors*; D005293:Ferritins / Q000378:metabolism; D046911:Macromolecular Substances; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016627:Oxidopamine / Q000032:analysis; D010300:Parkinson Disease / Q000378:metabolism*; D051381:Rats; D013378:Substantia Nigra / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D046911:Macromolecular Substances; D016627:Oxidopamine; D000255:Adenosine Triphosphate; D005293:Ferritins; D004298:Dopamine